Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of significant morbidity among hospitalized and community-dwelling persons. Initially described as a hospital- and healthcare-associated pathogen, new strains of community-associated MRSA (CA-MRSA) have emerged as an important cause of infection among of community-dwelling individuals. More recently CA-MRSA, as defined by pulsed-field gel electrophoresis, a form of DNA fingerprinting, has become a growing cause of healthcare-acquired infection. A large outbreak of infection caused by a highly pathogenic strain of CA-MRSA (USA300-0114) occurred at a large urban teaching hospital among post-partum women and newborns soon after discharge. Resistance to mupirocin was noted in a large proportion of isolates during the outbreak, which was an unusual and unexpected finding. Risk factors for colonization and infection with hospital-associated strains of MRSA (HA-MRSA) are fairly well established, but the risk factors for CA-MRSA colonization and infection in this high risk population remain poorly defined. By the use of novel, advanced statistical modeling, the current study aims to delineate the risk factors for colonization and infection with mupirocin-resistant and mupirocin-susceptible strains of CA-MRSA USA300-0114 during this outbreak. Given the dynamic nature of the newborn nursery, the setting in which transmission is suspected to have occurred, transmission dynamics and transmission rates will be determined using an open Susceptible-Infected-Recovered model. Finally, laboratory studies to determine the genetic makeup and other characteristics of the colonizing and infecting MRSA isolates will be performed in parallel with the clinical epidemiological investigations with the aim of determining mechanisms by which resistance to topical antimicrobial agents is spread and possible linkage between pathogen virulence and resistance. The proposed study will examine risk factors for colonization and infection in this population, however, some of the findings will likely be generalizable to CA-MRSA transmission in other populations both in the outbreak and non-outbreak setting. Furthermore, important information regarding development of resistance and mechanisms of resistance to topical agents commonly used in decolonization will be obtained. This information will ultimately have implications for the use of these agents in routine infection control and decolonization. PUBLIC HEALTH RELEVANCE: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), in particular MRSA clone USA300-0114, has rapidly become the most common cause of purulent skin and soft tissue infections in the United States. While initially associated with predominantly community-based disease and transmission, this pathogen has entered the hospital setting and now is a common cause of hospital-associated infection. The largest and most protracted outbreak of CA-MRSA infection among post-partum women and newborns occurred at a large urban teaching hospital in the fall of 2008 and continued through summer of 2010, with continued sporadic cases of carriage (nasal and skin) without infection since that time. The majority of infections were caused by MRSA USA300-0114, the most common strain of CA-MRSA. A high rate of resistance to mupirocin, an antibiotic used to eliminate carriage of MRSA, was noted. This study will investigate the epidemiologic risk factors predisposing to CA-MRSA colonization and infection among post-partum women and newborns. By using advanced statistical modeling techniques including time- series analysis, we will study risk factors associated with colonization and infection with CA-MRSA, and in particular colonization and infection with mupirocin-resistant CA-MRSA. In order to link the epidemiologic findings to the molecular and microbiological characteristics of the infecting bacteria recovered during this outbreak, analysis of plasmid DNA will be performed to determine the unique genetic features of the bacteria that may have enhanced the transmission of mupirocin resistance, enabled the acquisition of genetic elements imparting resistance to chlorhexidine and facilitated colonization during this outbreak.